psychologywikiaorg-20200213-history
Cell adhesion molecules
Cell Adhesion Molecules (CAM's) are proteins located on the cell surface involved with the binding with other cells or with the extracellular matrix (ECM) in the process called cell adhesion. These proteins are typically transmembrane receptors and are composed of three domains: an intracellular domain that interacts with the cytoskeleton, a transmembrane domain and an extracellular domain that interacts either with other CAMs of the same kind ('homophilic binding) or with other CAMs or the extracellular matrix (heterophilic binding). Families of CAMs Most of the CAMs belong to 4 protein families: Ig (immunoglobulin) superfamily (IgSF CAMs), the integrins, the cadherins and the selectins. IgSF CAMs Immunoglobulin SuperFamily CAMs (IgSF CAMs) are either homophilic or heterophilic and bind integrins or different IgSF CAMs. Here is a list of some molecules of this family: *NCAMs Neural Cell Adhesion Molecules *Intercellular adhesion molecules (ICAMs) *VCAM-1 Vascular Cell Adhesion Molecule *PECAM-1 Platelet-endothelial Cell Adhesion Molecule *L1 *CHL1 Selectins The selectins are a family of heterophilic CAMs that bind fucosylated carbohydrates, e.g. mucins . They are calcium-dependent. The three family members are E-selectin (endothelial), L-selectin (leukocyte) and P-selectin (platelet). The most well characterized ligand for the three selectins is P-selectin glycoprotein ligand-1 (PSGL-1), which is a mucin-type glycoprotein expressed on all white blood cells. Integrins :see also main article on Integrins The integrins are a family of heterophilic CAMs that bind IgSF CAMs or the extracellular matrix. They are heterodimers, consisting in two non-covalently linked subunits, called alpha and beta. 24 different alpha subunits are known that can link in many different combinations with the 9 different beta subunits, however not all combinations are observed. Cadherins :see also main article on Cadherins The cadherins are a family of homophilic CAMs, Calcium dependent. The most important members of this family are E-cadherins (epithelial), P-cadherins (placental) and N-cadherins (neural). Neurological Diseases Associated With CAM's Mental Retardation and other neurological disorders are attributable in part to disruption of normal cell adhesion Fetal Alcohol Syndrome (FAS) Commonalities between the neuropathology of some individuals with FAS and individuals expressing L1 mutations (i.e., mental retardation, dysgenesis of the corpus callosum) have led to the hypothesis that ethanol toxicity is mediated by alterations in cell adhesion molecules (reviewed in Ref. 130). A member of the Ig superfamily of cell adhesion molecules, L1 is posited in the CNS to mediate cell-cell interactions in developing tissue and adult tissue. Cell cultures using aggregation assays have demonstrated the disruptive effects of ethanol on L1-mediated cell-cell adhesion, at concentrations of ethanol that are clinically relevant, in NG108-15 neuroblastoma x glioma hybrid cells, cerebellar granule cells, and murine fibroblasts transfected with human L1 (67, 68, 70). In contrast, inhibition of cell aggregation by ethanol was not seen in Drosophila S2 cells expressing either neuroglian (i.e., the Drosophila form of L1) or human L1 (69), nor of adherence of J558L cells (i.e., MECHANISMS OF ETHANOL TERATOGENESIS 397 Ig-deficient mouse myeloma cells) to L1-coated surfaces following 10 mM or 100 mM ethanol (66). These data suggest that the effects of ethanol on cell adhesion may be cell-type dependent (70). The interaction of ethanol with L1 may also alter neuronal outgrowth. In cerebellar granule cell cultures, shorter neurite outgrowth was observed 8 to 12 hrs after administration of 20 mM ethanol compared to controls (66). More recently, Watanabe and colleagues replicated this finding and demonstrated that ethanol-induced inhibition of neurite outgrowth signaled through extracellular signalregulated kinase (ERK) and phospholipase D pathways (131). For reference information see: Goodlett, C. R., Horn, K. H., & Zhou, F. C. (2005). Alcohol Teratogenesis: Mechanisms of Damage and Strategies for Intervention. See also *Cadherin *Cell adhesion *Extracellular matrix *Integrin *Neural cell adhesion molecule *Transmembrane receptorsCategory:Cell biology Category:Transmembrane receptors Category:Signal transduction Category:Membranes Category:Integral membrane proteins Category:Cell adhesion proteins